During this initial period, the controlled cortical impact (CCI) model of TBI was set up along with behavioral tests to evaluate the TBI-induced functional deficits. Significant motor deficits assessed by the accelerating rotarod and beam walk tests were noticed at 24h after TBI, however, these motor deficits were transient in nature and restored later in time. A dietary condition to generate extreme DHA depletion in the mouse brain was established by rearing mice on an omega-3 fatty acid deficient diet for three generations. The brain DHA level in the third generation omega-3 deficient animals was lowered by over 70%, which was mostly compensated by the increase of docosapentaenoic acid (DPA, 22:5n-6). Age and gender matched mice at 10-12 weeks from adequate and deficient groups were subjected to the CCI procedure and the TBI-induced motor deficits were evaluated. We found that the motor function of omega-3 adequate animals assessed by the rotarod test was recovered by day 2 after TBI while the deficient group showed prolonged motor deficit until day 4 after TBI. The difference in spontaneous recovery between two groups is statistically significant (p<0.01). Similarly, the percent foot slips from the balance beam were significantly greater (p<0.05) in the TBI-inflicted deficient groups from days 2 to 7 post surgery. Further tests are being performed to evaluate cognitive deficit, as deficient and adequate animal pairs become available. For the analysis of TBI-induced formation of metabolites in mouse brains with different DHA status, we have established a metabolite profiling method using the multiple reaction monitoring mode (MRM) by HPLC-electrospray ionization (ESI)-MS/MS. Using this method, we first characterized the TBI-induced production time course for the endogenous metabolites of AA and DHA. During the first 24h, PGE2, PGD2, 12-hydroxyeicosatetraenoic acid (12-HETE) and 14-hydroxydocosahexaenoic acid (14-HDHE) were significantly increased in the TBI-inflicted brains. We also observed a significant elevation of N-docosahexaenoylethanolamine (synaptamide), a previously characterized neuritogenic and synaptogenic derivative of DHA, by 24h after TBI in comparison to the sham operated controls. Neuritogenic effects of DHA and synaptamide were confirmed in cultured neurons from the cortical region which would be most significantly inflicted by the CCI procedure.